ABSTRACT
BACKGROUND: Pulmonary hypertension "PH" is considered a serious cardiovascular disease. World Health Organization divided PH into groups depending on many factors like pathological, hemodynamic, and clinical pictures. Lately, various micro-RNAs "miRNAs" and other novel biomarkers like endoglin and asymmetric dimethylarginine "ADMA" might have a role in diagnosis of PH and may differentiate between pulmonary arterial hypertension "PAH" and non-PAH. The purpose of the study is to show the role of miR-21, miR-124, endoglin and ADMA in the diagnosis of PH and distinguishing between WHO group 1 PH and WHO group 2 and 3 PH and to identify patients who might benefit from non-invasive and inexpensive tools to diagnose PAH. RESULTS: miR-21 was upregulated in group 1 PH, and there was significant difference between group 1 PH as compared with group 2 PH, group 3 PH and control; miR-124 was down-regulated in group 1 PH with highly significant difference between group 1 and group 2 PH and control but no significant difference with group 3 PH, endoglin was elevated in group 1 PH with a significant difference as compared to group 2 PH, group 3 PH and control. ADMA was elevated in group 1 PH as compared to control; however, there was no significant difference between it and group 2, 3 PH. CONCLUSIONS: miR-21, miR-124, endoglin and ADMA are good biomarkers to diagnose PH; however, only miR-21 and endoglin could distinguish group 1 PH from group 2 and 3 PH.
ABSTRACT
BACKGROUND: Driver molecular aberrations, such as epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK) gene rearrangement, play an important role in the oncogenesis and progression of non-squamous non-small-cell lung cancers (NSCLC). Therefore, this study aimed to detect the incidence of driver mutations among non-squamous NSCLC. PATIENTS AND METHODS: This was a retrospective-prospective cohort study on 131 patients with non-squamous NSCLC. Data on age, smoking status, chest symptoms, method of lung cancer diagnosis, molecular testing, including EGFR mutations in formalin-fixed paraffin-embedded (FFPE) tumor tissue and serum circulating tumor DNA using next-generation sequencing and ALK gene rearrangement by FFPE tumor tissue, and follow-up data regarding treatment modalities and outcomes were collected. RESULTS: The median age of the patients was 57 years (range: 32-79 years). Out of 131 patients, 97 were males (74%), and 90 (68.7%) were smokers. Among 128 patients tested, 16 (12.5%) had EGFR mutations detected with either technique by formalin-fixed paraffin-embedded (FFPE) tumor tissue or/and serum circulating tumor DNA using next-generation sequencing, and 6 (4.7%) had ALK rearrangement by FFPE tumor tissue. The majority (62.6%) presented with metastatic disease. Among the 102 patients who received first-line systemic therapy, the objective response rate was 50.0% in mutated NSCLC versus 14.6% in non-mutated (p < 0.001). Among the eight mutated patients who received first-line tyrosine kinase inhibitors (TKIs), 7 patients achieved either complete response or partial response. Among the 22 mutated patients, the median overall survival was 3 months in those who did not receive targeted therapy versus not reached in those who received any type of targeted therapy (p < 0.001). CONCLUSION: Screening patients with newly diagnosed non-squamous NSCLC for driver mutations is essential for major prognostic and therapeutic implications. Early administration of TKIs in mutated patients significantly improves disease outcomes.
